Tri-tert-butylphosphine tetrafluoroborate → methyl 8-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-pyrazolo[5,1-a]isoquinoline-7-carboxylate

HRID 595099Notes

Reaction equation

HRID 595099 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[CH:22]=[CH:21][C:20]2[C:19]3=[CH:23][CH:24]=[N:25][N:18]3[CH:17]=[CH:16][C:15]=2[C:14]=1[C:26]([O:28][CH3:29])=[O:27])(=[O:11])=[O:10].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[CH2:48]([N:50]([CH2:67][CH3:68])[CH2:51]/[CH:52]=[CH:53]\[Sn](CCCC)(CCCC)CCCC)[CH3:49]>O1CCOCC1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:48]([N:50]([CH2:67][CH3:68])[CH2:51]/[CH:52]=[CH:53]\[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[CH:22]=[CH:21][C:20]2[C:19]3=[CH:23][CH:24]=[N:25][N:18]3[CH:17]=[CH:16][C:15]=2[C:14]=1[C:26]([O:28][CH3:29])=[O:27])(=[O:11])=[O:10])[CH3:49]

Participants

7

Reactant 3

HCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 70984312Methyl 8-(2-bromo-4-fluorobenzenesulfonylamino]-pyrazolo[5,1-a]isoquinoline-7-carboxylate2×HCID 86684726N,N-diethyl-N-((Z)-1-tributylstannanylprop-1-en-3-yl)amine2×

Product 1

HCID 86712812methyl 8-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-pyrazolo[5,1-a]isoquinoline-7-carboxylateYield 27.3%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of methyl 8-(2-bromo-4-fluorobenzenesulfonylamino]-pyrazolo[5,1-a]isoquinoline-7-carboxylate (Intermediate 2, 0.103 g), tris-(dibenzylideneacetone)-dipalladium (0) (0.025 g), tri-tert-butylphosphonium tetrafluoroborate (0.0127 g) and N,N-diethyl-N—((Z)-1-tributylstannanylprop-1-en-3-yl)-amine (Intermediate 3, 0.265 g) in dioxane (3 mL) was irradiated in the microwave at 80° C. for 2 hours. After cooling, the mixture was diluted with ethyl acetate and filtered through Celite. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-20% to give methyl 8-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-pyrazolo[5,1-a]isoquinoline-7-carboxylate (0.030 g).

Workup

  1. customwas irradiated in the microwave at 80° C. for 2 hours
  2. temperatureAfter cooling
  3. filtrationfiltered through Celite
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue was purified by chromatography on silica
  6. washeluting with a mixture of methanol and DCM with a gradient of 0-20%

Sources & evidence

ORD record
ord-101f81e24a1848abb6d131c79ccad484
Source dataset
uspto-grants-2016_01
Patent number
US09242997B2

Reaction notes

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